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Start-up lifting barrier to getting medicine to brain
Inventors on verge of breakthrough
By Tim Wacker, Globe Correspondent | May 11, 2006
The 15-foot-square cubicle in the Wannalancit Mill building that Perfusion Technology calls a lab doesn´t look like an incubator for a major medical breakthrough
Two chairs and a counter of scientific gadgets suggest the company is into something more than market research. Yet two local medical device inventors working there might be on the verge of a revolution in neuroscience, according to specialists familiar with their work.
Ulrich Herken of Medford and Al Kyle of Andover think they´ve found a way to get medicine past the so-called blood-brain barrier, arguably the biggest hurdle in treating brain diseases without a scalpel.
Through the use of ultrasound high-frequency sound waves humans can´t hear, the two men say, they can lower this barrier in brain blood vessels enough for medicines to get through to where they couldn´t before.
The procedure is simple, Herken said. Ultrasound-emitting devices are positioned on a patient´s head to target a specific area. The machine is turned on, and shortly afterward, medicine is administered intravenously. Then the ultrasound is shut off and the blood-brain barrier goes back up.
Outside of the earlier work in Germany, their treatment is largely untested in humans. Should it bear fruit in clinical trials with humans, it will open a whole new world of treatments for such intractable illnesses as epilepsy, Parkinson´s disease, Alzheimer´s, and brain cancer.
All blood vessels are lined with cells that regulate the flow of food and oxygen from the blood to the tissues that need them. In the brain, these cells are packed much closer together, providing a finer filter against any unwanted substances, like toxins, that make it into the blood system. But that also prevents medications from working on the brain.
´´I´m very hopeful and encouraged by what they have. There will be great demand if this holds up in clinical trials," said Dr. Antonio Chiocca, chairman of the neurological surgery department at Ohio State University Medical Center.
Chiocca collaborated with Herken and Kyle on research at Massachusetts General Hospital two years ago, and the three have been working together at Ohio State through a federal grant that Perfusion received last year.
´´Clearly, the ability to disrupt the blood-brain barrier is the Holy Grail of drug delivery to the brain," he said. ´´I think they have a good concept and some excellent results. How it´s finally used may lead to something very important."
All this came quite unexpectedly from research the two entrepreneurs undertook for a small Andover-based company they helped start eight years ago called Walnut Technologies. They thought then that ultrasound could be used to improve blood flow to the brain for stroke victims.
That treatment was more problematic than promising, and Walnut folded in 2003. But just as their work was shutting down, the two men discovered ultrasound´s effect on lowering the blood-brain barrier.
Two chairs and a counter of scientific gadgets suggest the company is into something more than market research. Yet two local medical device inventors working there might be on the verge of a revolution in neuroscience, according to specialists familiar with their work.
Ulrich Herken of Medford and Al Kyle of Andover think they´ve found a way to get medicine past the so-called blood-brain barrier, arguably the biggest hurdle in treating brain diseases without a scalpel.
Through the use of ultrasound high-frequency sound waves humans can´t hear, the two men say, they can lower this barrier in brain blood vessels enough for medicines to get through to where they couldn´t before.
The procedure is simple, Herken said. Ultrasound-emitting devices are positioned on a patient´s head to target a specific area. The machine is turned on, and shortly afterward, medicine is administered intravenously. Then the ultrasound is shut off and the blood-brain barrier goes back up.
Outside of the earlier work in Germany, their treatment is largely untested in humans. Should it bear fruit in clinical trials with humans, it will open a whole new world of treatments for such intractable illnesses as epilepsy, Parkinson´s disease, Alzheimer´s, and brain cancer.
All blood vessels are lined with cells that regulate the flow of food and oxygen from the blood to the tissues that need them. In the brain, these cells are packed much closer together, providing a finer filter against any unwanted substances, like toxins, that make it into the blood system. But that also prevents medications from working on the brain.
´´I´m very hopeful and encouraged by what they have. There will be great demand if this holds up in clinical trials," said Dr. Antonio Chiocca, chairman of the neurological surgery department at Ohio State University Medical Center.
Chiocca collaborated with Herken and Kyle on research at Massachusetts General Hospital two years ago, and the three have been working together at Ohio State through a federal grant that Perfusion received last year.
´´Clearly, the ability to disrupt the blood-brain barrier is the Holy Grail of drug delivery to the brain," he said. ´´I think they have a good concept and some excellent results. How it´s finally used may lead to something very important."
All this came quite unexpectedly from research the two entrepreneurs undertook for a small Andover-based company they helped start eight years ago called Walnut Technologies. They thought then that ultrasound could be used to improve blood flow to the brain for stroke victims.
That treatment was more problematic than promising, and Walnut folded in 2003. But just as their work was shutting down, the two men discovered ultrasound´s effect on lowering the blood-brain barrier.
At the time, they returned to the United States more disappointed in Walnut´s failure than optimistic about the future of their new discovery. But slowly, the potential started to sink in. They went back to Andover, where they set up shop in Kyle´s garage.
´´When we´d first found that we´d penetrated the blood-brain barrier, that was thought to be terrible, an adverse event, so the company went out of business," Kyle said. ´´But then Uli and I thought about this and realized this could be good, that we could treat people with this."
There are drugs that now are nearly useless but could be effective in treating Parkinson´s, stroke, Alzheimer´s, and epilepsy, if they could just get past the blood-brain barrier, Herken said. Cancer medicines could open whole new world of options in fighting brain tumors through the same treatment.
´´The terrible thing about brain cancer is there are hardly any treatment options available," Herken said. ´´Drugs that can prevent cancer from spreading in the rest of the body don´t get into the brain. The brain is, unfortunately, a safe haven for cancer."
There are still many hurdles Perfusion must pass before any such medical miracles happen. For the past year, their research has fine-tuned delivering the beam to targeted areas.
In the process, Perfusion has moved from Kyle´s garage to a mill building in Lawrence to their current digs in Lowell. The are using a plastic tub of water, an array of animal skulls, and a variety of ultrasonic hardware in an effort to simulate the real thing: humans.
Hardly the sort of circumstances that lead to medical breakthroughs. The only similar research going on in this country involves a team of researchers at Brigham and Women´s Hospital, Kyle said. The hospital is using a high-powered pinpoint beam of ultrasound, which entails problems that need to be worked out, including getting past federal regulators. Using low-powered ultrasound, Perfusion can treat a large or small a section of the brain with a safer beam the agency might look more kindly on, he says.
´´This is a gentler, reversible method," Herken said. ´´And we´re pretty good at controlling where this stuff goes and how much of it gets there. It actually works, and it appears to be safe."
Appearances can be deceiving, and Perfusion needs proof if it´s to break into the US markets. Another German clinic has shown an interest in conducting human trials of this new technology on its brain cancer patients.
They will let Perfusion administer ultrasound in conjunction with cancer-curbing medicines in patients about to undergo brain surgery for their tumors. Once removed, the tumors will be analyzed to see how much of the medicine was taken up.
If the medicine is found in the tumors, the two men will return home considerably happier than the last time they left Germany.
´´People don´t pay any attention to animal studies; they pay attention to the human stuff," Kyle said. ´´If you can deliver drugs to the brain, you can just wait for the phone to ring, there are so many therapies that you can pursue."
Those calls will hopefully be coming from interested investors. Since its founding, Perfusion has been squeaking by on grants too small to fully fund such lofty work, and money is needed right now to get to Germany.
However, there is some promise. Perfusion will be the first tenant of new lab space opening at the Lowell campus of the University of Massachusetts specifically to house start-up companies researching medical devices.
And a scientific paper discussing ultrasound´s effect on the blood-brain barrier was just published, giving Walnut Technologies credit for the discovery, Kyle said. A Parkinson´s research foundation run by actor Michael J. Fox, who has the disease, is also showing an interest in Perfusion´s work.
´´That´s the thing about being a start-up company," Herken said. ´´You get to have a lot more fun, but you are always looking for money."
If all goes well at new trials in Germany, the company will begin the process of obtaining FDA approval and could have the treatment available to the public as early as 2010, Herken said.
´´It´s really important to go through this testing process," he said. ´´You´ve got to be aware of the risks so you can know how to put [the treatment] to its best use."
© Copyright 2006 Globe Newspaper Company.